1 / 28

MYELOMA AND THE KIDNEY

MYELOMA AND THE KIDNEY. DIAGNOSIS TREATMENT PROGNOSIS. MYELOMA. Monoclonal expansion of plasma cell population Incidence ~5 per 100,000 Median age 69 male, 71 female 5% <40 years at diagnosis; 10-15% <50 years. Diagnostic Criteria 1. MAJOR plasmacytoma on tissue biopsy

hillary
Download Presentation

MYELOMA AND THE KIDNEY

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. MYELOMA AND THE KIDNEY • DIAGNOSIS • TREATMENT • PROGNOSIS

  2. MYELOMA • Monoclonal expansion of plasma cell population • Incidence ~5 per 100,000 • Median age 69 male, 71 female • 5% <40 years at diagnosis; 10-15% <50 years

  3. Diagnostic Criteria 1 • MAJOR • plasmacytoma on tissue biopsy • bone marrow plasmacytosis >30% • monoclonal globulin elevation on electrophoresis • >35 g/l for IgG • >20 g/l for IgA • >1 g/ 24hrs of kappa/lambda light chainsin urine

  4. Diagnostic Criteria 2 • MINOR • bone marrow plasmacytosis 10-30% • monoclonal globulin elevation (< major) • lytic bone lesions • immune paresis • DIAGNOSIS 1 major + 1 minor

  5. Staging • Durie & Salmon; Cancer 1975 • 1. Low myeloma mass Hb >10g/l; Ca normal; 1 or less osteolytic lesions • 2. Intermediate (fits neither 1. nor 2.) • 3. High myeloma mass Hb <8.5g/l; Ca elevated; multiple osteolytic lesions

  6. Prevalence of Renal Failure 1 • Knusden; Eur. J. Haem. 2000 • 775 myeloma patients; 1984-86, 1990-92 • 29% had creatinine >130 • 58% achieved normal creatinine in 1 year • recovery more likely if : moderate ARF, hypercalcaemia; low BJP mass

  7. Prevalence of Renal Failure 2 • in multivariate analysis independent prognostic factors for survival : renal failure age stage 3 disease hypercalcaemia • median survival of those dialysed 3.5 months

  8. Prevalence of Renal Failure 3 • MRC Myeloma Trial, BMJ, 1994 • 998 patients under 75 years • 1982-91 • 43% creatinine >130

  9. Renal Disease in Myeloma • “Myeloma Kidney” or Cast Nephropathy • Renal Tubular Dysfunction • Amyloidosis • Cryoglobulinaemia • Hypercalcaemia • ARF with radiocontrast agents

  10. Immunoglobulin light chains (or Bence-Jones proteins) 1 • kappa or lambda • molecular weight ~22,000 • freely filtered in glomeruli • normal rate <30mg/day of light chain excretion • re-absorbed in proximal tubule • not detected by urinary dipstick • bind to Tamm-Horsfall mucoprotein • in myeloma 100mg-30 g/day

  11. Immunoglobulin light chains (or Bence-Jones proteins) 2 • Direct tubular toxicity • Intra-tubular cast formation and obstruction • Variable nephrotoxic potential (cast nephropathy, amyloidosis, no renal disease)

  12. “Myeloma Kidney” • “acute or chronic renal failure that results from the filtration of monoclonal immunoglobulin light chains” • tubular toxicity • intra-tubular cast formation and obstruction

  13. TREATMENT • Rehydration • Urine Alkalinisation • Loop Diuretics • Chemotherapy • Plasmapheresis • Dialysis

  14. Rehydration • isotonic solutions • hypercalcaemia • contrast examinations • treat infection; stop nephrotoxins

  15. Urine Alkalinisation • Huang, Lab. Invest. 1993 • Tamm-Horsfall solubility reduced at low pH • acidic environment increases light-chain/THMP binding • forced alkaline diuresis >3 l/day with urinary pH >7

  16. Loop Diuretics • may have a role if hypercalcaemia present • “wash out” obstructing casts • Sanders, J. Clin. Invest. 1992 • in rats diuretics increase tubular Na conc.. which promotes THMP aggregation

  17. Chemotherapy • to reduce light-chain production • melphalan, cyclophosphamide, steroids • VAD (vincristine, doxorubicin) • myeloablation with autologous BMT or blood stem-cell transplant • response rate similar whether renal failure or not

  18. Plasmapheresis 1 • effective in rapidly reducing serum light-chain load • no effect on light-chain production • short-acting as light-chains throughout ECF • efficacy not fully established

  19. Plasmapheresis 2 • Johnson; Arch. Int. Med. 1990 • prospective , randomised trial of plasmapheresis • 21 patients with active myeloma + renal failure • all had renal biopsy • 10- alkaline diuresis, chemotherapy • 11- alkaline diuresis, chemo, plasmapheresis

  20. Plasmapheresis 3 • 5 patients on dialysis, 3 recovered renal function all of whom had TPE • 16 non-dialysis patients, 5 in first group and 7 in second group showed improvement in renal function

  21. Plasmapheresis 4 • Zucchelli, K.I. 1988 • prospective , randomised trial • 29 patients, BJP >1g/day • 24 required RRT • 15- chemo, plasmapheresis, +/- HD • 14- chemo, +/- PD

  22. Plasmapheresis 5 • Group 1 13/15 recovered renal function 68% 1 year survival • Group 2 2/14 recovered renal function 28% 1 year survival 5 deaths before 2 months

  23. Renal Replacement Therapy • No trials comparing PD/HD • both modalities remove small amount of light-chains

  24. Renal Replacement Therapy • Korzets, Am. J. Kid. Dis. 1990 • 10 patients with myeloma + ESRF (all on PD) • Survival from diagnosis- 32+/- 24 months from start RRT- 25+/- 20 months 5 responded to chemo- 47+/- 25 months 5 non-responders- 17+/- 7 months

  25. Renal Replacement Therapy • Iggo, Q. J. Med. 1989 • 23 patients, 11 presented with ESRF • 15 died during study • actuarial survival 45% at 1 year • 6 still alive at 2 years • HD/PD “equally effective” • peritonitis a common problem

  26. Outcomes and Prognosis 1 • Rota, Medicine 1987 • 34 patients, myeloma + creatinine >300 • 16 recovered renal function • 18 did not, 9 required dialysis • fewer females recovered • 88% had biopsy; recovery only if ATN or typical cast nephropathy • recovery may be delayed (months)

  27. Outcomes and Prognosis 2 • 6 further studies • 151 patients • % renal recovery 51% (mean; 17-83) • median survival 17 months (9-22) • Alexanian, Arch. Int. Med.. 1990 • 494 consecutive myeloma patients • presence/degree renal failure not predictive for survival

  28. Outcomes and Prognosis 3 • Clark; Blood Rev. 1999 • renal impairment present in ~50% • dialysis now accepted treatment (ARF + CRF) • renal failure not a contra-indication to aggressive treatment (autologous BMT; stem-cell transplant) • outcome similar to those without renal impairment

More Related